Last week FDA approved tbo-filgrastim, a recombinant human granulocyte colony-stimulating factor (or “G-CSF”) produced by Sicor Biotech, a Lithuanian subsidiary of Teva Pharmaceutical Industries. tbo-filgrastim approval letter Teva press release. Amgen has sold billions of dollars of its recombinant G-CSF called Neupogen® since approval in 1991. While Amgen has exclusive rights in the U.S., Teva and others have been selling G-CSF products in Europe for several years. Under the terms of a 2011 patent litigation settlement between Amgen and Teva, Teva’s product should launch in the U.S. in November 2013.
As we addressed in an earlier post , Teva filed for approval of its G-CSF product before the U.S. biosimilar pathway was available. Thus, Teva submitted a full BLA for its product. In its press release, made it clear that it does not deem it to be biosimilar to Neupogen: “FDA has not approved tbo-filgrastim as a biosimilar to Neupogen (filgrastim), which is a previously licensed biological product that contains a related drug substance.” Teva currently markets filgrastim in Europe under the trade name Tevagrastim, which is approved as a biosimilar to Neupogen®. Returning to the U.S. BLA, comparison of the product inserts for the two products is interesting. Tbo-filgrastim is approved for similar indications:
Click here to view table.
The adverse reactions and warnings and precautions are also similar between the two labels. Also it appears that the phase three clinical trials included approximately the same number of patients. Also, no comparison studies to establish any superiority were included in the BLA. And, even though Neupogen® has been marketed for 20 years, FDA has required extensive post-marketing studies including development of an assay for neutralizing antibodies and a 426-person clinical study assessing anti-G-CSF antibody formation. Approval letter <> So essentially FDA did not allow Teva to cut any corners compared to the Neupogen® regulatory package.
Although not a biosimilar per se, Teva’s approach to marketing tbo-filgrastim in the U.S. will be a guidepost for the nascent U.S. biosimilar industry. Other than the fact that Teva will not be able to make any comparability claims, market conditions for tbo-filgrastim will be similar to biosimilars. So presumably, Teva’s approach and eventual experience with marketing, pricing, reimbursement, patient education, and post-marketing monitoring will inform biosimilar manufacturers. And, tbo-filgrastim’s market share dynamics and financial performance should allow industry watchers to better predict the performance of biosimilars when they arrive.
One does wonder though, will prescribers prefer a “me-too” drug with completely independent proof of safety and efficacy, or a biosimilar whose performance has been validated against the established brand product? It is not inconceivable that Teva is or will go back to FDA to acquire biosimilar or interchangeable status in order to better compete against Neupogen® and the biosimilars when they come.